Novel N-substituted indole Schiff bases as dual inhibitors of cyclooxygenase-2 and 5-lipoxygenase enzymes: Synthesis, biological activities in vitro and docking study

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61389030%3A_____%2F16%3A00465178" target="_blank" >RIV/61389030:_____/16:00465178 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/61989592:15310/16:33159390

Výsledek na webu

<a href="http://dx.doi.org/10.1016/j.ejmech.2016.08.013" target="_blank" >http://dx.doi.org/10.1016/j.ejmech.2016.08.013</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1016/j.ejmech.2016.08.013" target="_blank" >10.1016/j.ejmech.2016.08.013</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Novel N-substituted indole Schiff bases as dual inhibitors of cyclooxygenase-2 and 5-lipoxygenase enzymes: Synthesis, biological activities in vitro and docking study

Popis výsledku v původním jazyce

Two new series of N-substituted indole derivatives 4a-1 and 5a-h were synthesized. Their chemical structures were confirmed using spectroscopic tools including IR, H-1 NMR,C-13 NMR mass spectroscopy and elemental analyses. The results showed no significant cytotoxic activity on either cancer or normal human cells. Anti-inflammatory activity for all target compounds was evaluated in vitro. Compounds 5a -h were found to have better anti-inflammatory activity than 4a-1. The inhibitory activity of COX-2 and 5-LOX were tested for 5a-h. Three compounds, 5c, 5d and 5f showed excellent COX-2 inhibitory activity with IC50 ranging from 0.98 to 1.23 mu M compared to the reference celecoxib (1.54 mu M). These compounds had a reasonable selectivity index between 7.03 and 8.05. Additionally, p-methylbenzoyl derivative 5g (IC50 = 5.78 M) had superior 5-LOX inhibitory activity, higher than quercetin. 5e was close to quercetin in its LOX inhibitory activity. Compounds 5a h were docked inside the active site of COX-2 and 5-LOX enzymes.

Název v anglickém jazyce

Novel N-substituted indole Schiff bases as dual inhibitors of cyclooxygenase-2 and 5-lipoxygenase enzymes: Synthesis, biological activities in vitro and docking study

Popis výsledku anglicky

Two new series of N-substituted indole derivatives 4a-1 and 5a-h were synthesized. Their chemical structures were confirmed using spectroscopic tools including IR, H-1 NMR,C-13 NMR mass spectroscopy and elemental analyses. The results showed no significant cytotoxic activity on either cancer or normal human cells. Anti-inflammatory activity for all target compounds was evaluated in vitro. Compounds 5a -h were found to have better anti-inflammatory activity than 4a-1. The inhibitory activity of COX-2 and 5-LOX were tested for 5a-h. Three compounds, 5c, 5d and 5f showed excellent COX-2 inhibitory activity with IC50 ranging from 0.98 to 1.23 mu M compared to the reference celecoxib (1.54 mu M). These compounds had a reasonable selectivity index between 7.03 and 8.05. Additionally, p-methylbenzoyl derivative 5g (IC50 = 5.78 M) had superior 5-LOX inhibitory activity, higher than quercetin. 5e was close to quercetin in its LOX inhibitory activity. Compounds 5a h were docked inside the active site of COX-2 and 5-LOX enzymes.

Druh

J_x - Nezařazeno - Článek v odborném periodiku (Jimp, Jsc a Jost)

CEP obor

EB - Genetika a molekulární biologie

OECD FORD obor

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Projekt

<a href="/cs/project/LO1204" target="_blank" >LO1204: Udržitelný rozvoj výzkumu v Centru regionu Haná</a><br>

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2016

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

European Journal of Medicinal Chemistry

ISSN

0223-5234

e-ISSN

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Svazek periodika

123

Číslo periodika v rámci svazku

NOV 10

Stát vydavatele periodika

FR - Francouzská republika

Počet stran výsledku

11

Strana od-do

803-813

Kód UT WoS článku

000385319000064

EID výsledku v databázi Scopus

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